Biomedical subjects

Hong Xue

Publications and source records attributed to Hong Xue.

At least 19 recordsLinked to original sources

PubMed2006

The evolution of GABAA receptor-like genes.

The inhibitory ligand-gated ion channel family of receptors, including the type A gamma-aminobutryic acid (GABA(A)) and glycine receptors, mediates inhibitory neurotransmissions in the central nervous system. In this study, GABA receptor (GABR) evolution was explored through comparative genomics using genomes that span divergent lineages. GABA(A)/Gly receptor-like (GRL) gene sequences were retrieved from the genomes of various species ranging from mammal to fish to worm and subjected to cross-species comparison. All vertebrate GRL gene sets in the study but no invertebrate ones exhibit the extensive and conserved pattern of gene clustering that is characteristic of human GABR genes, indicating that the gene clusters were established early in vertebrate evolution, after divergence from the invertebrates. Moreover, the vertebrate gene structure is highly conserved with a basic 9-coding exon structure, whereas, as well as being diverse in copy numbers and chromosomal loci, the invertebrate GRL genes display a variety of gene structures. Remarkably, the invertebrates each possess a unique GRL gene pair that lies in neighboring loci within their respective genomes: zc482.5 and zc482.1 in roundworm, CG8916 and CG17336 in fruitfly, Ci4249 and Ci4254 in Ciona, and these were revealed by phylogenetic analysis to be homologous to human GABR alpha and beta subunits, respectively. The phylogenetic classification of these genes is also corroborated by experimental ligand-binding measurements using recombinant gene products. Furthermore, the 3 invertebrate gene pairs harbor characteristic key residues and exhibit similarities in intron positions to their vertebrate counterparts. The results strongly indicate that such a gene pair originally existed in the bilaterian ancestor from which all 3 phyla evolved and suggest that the extant GABR clusters arose from an ancestral alpha-beta subunit gene pair gave rise to the extant GABR clusters.

Amino Acid Sequence↗

PubMed2006

Alkylene tether-length dependent gamma-aminobutyric acid type A receptor competitive antagonism by tacrine dimers.

Bis(7)-tacrine was previously demonstrated as an antagonist of gamma-aminobutyric acid type A (GABA(A)) receptors. In this study, the effects of a series of alkylene-linked tacrine dimers on GABA(A) receptors were examined. In radioligand binding assay, the analogues differed in binding affinity for GABA(A) receptors, and potency monotonically increased as the tether was shortened from nine to two methylenes. Bis(2)-tacrine, the shortest tacrine dimer, could displace [(3)H]muscimol from rat brain membranes with an IC(50) of 0.48 microM, which was 11, 13 and 525 times more potent than the GABA(A) receptor antagonist (+)-bicuculline, bis(7)-tacrine and tacrine, respectively. In whole-cell patch-clamp recordings, these dimeric tacrine analogues competitively antagonized GABA-induced inward current with a rank order of potency of bis(2)-tacrine>bicuculline>bis(7)-tacrine>bis(9)-tacrine>tacrine, and the potency of bis(2)-tacrine was 11, 18 and 487 times higher than that of (+)-bicuculline, bis(7)-tacrine and tacrine, respectively. Bis(2)-tacrine shifted the GABA concentration-response curve to the right in a parallel manner, and the inhibition was voltage-independent between -80 and +20 mV. It can be concluded that the shorter the alkylene linkage in tacrine dimers the stronger the binding affinity and higher the antagonistic effect on the GABA(A) receptor will be.

Alkylation↗

PubMed2006

GABRB2 association with schizophrenia: commonalities and differences between ethnic groups and clinical subtypes.

BACKGROUND: Single nucleotide polymorphisms (SNPs) and haplotypes in intron 8 of type A gamma-aminobutyric acid (GABA(A)) receptor beta2 subunit gene (GABRB2) were initially found to be associated with schizophrenia in Chinese. This finding was subjected to cross-validation in this study with Japanese (JP) and German Caucasian (GE) subjects. METHODS: Single nucleotide polymorphisms discovery and genotyping were carried out through resequencing of a 1839 base pair (bp) region in GABRB2. Tagging SNPs (tSNPs) were selected based on linkage disequilibrium (LD), combinations of which were analyzed with Bonferroni correction and permutation for disease association. Random resampling was applied to generate size- and gender-balanced cases and control subjects. RESULTS: Out of the 17 SNPs (9.2/kilobase [kb]) revealed, 6 were population-specific. Population variations in LD were observable, and at least two low LD points were identified in both populations. Although disease association at single SNP level was only shown in GE, strong association was demonstrated in both JP (p = .0002 - .0191) and GE (p = .0033 - .0410) subjects, centering on haplotypes containing rs1816072 and rs1816071. Among different clinical subtypes, the most significant association was exhibited by systematic schizophrenia. CONCLUSIONS: Cross-population validation of GABRB2 association with schizophrenia has been obtained with JP and GE subjects, with the genotype-disease correlations being strongest in systematic schizophrenia, the most severe subtype of the disease.

Adult↗

PubMed2006

[Therapeutic effect of a novel recombinant vaccine encoding chicken collagen type II procollagen gene on collagen-induced arthritis in rat].

OBJECTIVE: To investigate the therapeutic effect of gene vaccine encoding chicken collagen type II (CC II) on collagen-induced arthritis (CIA) comprehensively. METHODS: Three groups (CIA) were given a single intravenous injection of plasmid pcDNA-CCOL2A1 (20 microg/kg, 200 microg/kg, 400 microg/kg) respectively and one group (CIA) was injected 200 microg/kg pcDNA3.1 as a control. The effect of gene vaccine (pcDNA-CCOL2A1) was evaluated according to the arthritis score, radiological and histological examinations. RESULTS: The severity of arthritis of CIA rats which were administered 200 microg/kg pcDNA-CCOL2A1 was significantly reduced from the fifth day. According to the radiological and histological examinations, the articular cartilage as well as subchondral bone trabeculae are similar to those of the normal groups, so the bone and articular cartilage structure were protected after treatment with 200 microg/kg pcDNA-CCOL2A1 with a little synovial hyperplasia. The therapeutic effect of 200 microg/kg pcDNA-CCOL2A1 group has significant difference in comparison with that of the pcDNA3.1 group (P < 0.05) and the arthritis scores are reduced to about 50% of those in control groups, but 20 microg/kg group and 400 microg/kg group has no therapeutic effect in our observation (P > 0.05). CONCLUSION: The new gene vaccine pcDNA-CCOL2A1 has significant therapeutic effect on CIA rats, and the treatment may therefore be an effective strategy for RA patient clinically.

Animals↗

PubMed2006

Identification of lipid binding and lipoprotein lipase activation domains of human apoAV.

ApoAV, a newly discovered apolipoprotein, plays a key role in human triglyceride homeostasis; however, the structure-function correlation of apoAV is not clearly understood. To explore the relationship, wild type and six deletion mutants, that is (AV (Delta(1-51)), AV (Delta(51-128)), AV (Delta(132-188)), AV (Delta(192-238)), AV (Delta(246-299)), AV (Delta(301-343))), of human apoAV expressed in Escherichia coli were studied. All the deleted regions together encompass almost the entire 343 amino acid sequence of wild type apoAV. Circular dichroism spectroscopy showed that the alpha helical content of lipid-free wild type apoAV was 46%. In comparison with wild type apoAV, AV (Delta(192-238)) and AV (Delta(301-343)) displayed significantly decreased lipid binding activities, confirming the importance of these two regions in lipid binding function of apoAV. While, the LPL activation function of apoAV remarkably impaired after deletion of residues 192-238. These findings suggested that the domain (192-238) is absolutely necessary for apoAV in lipid binding and lipoprotein lipase activation.

Animals↗

PubMed2006

Analysis of GABRB2 association with schizophrenia in German population with DNA sequencing and one-label extension method for SNP genotyping.

OBJECTIVES: Schizophrenia (SCZ) is a complex mental disease that affects approximately 1% of the population. In this study, six SNPs in GABRB2 were genotyped for a case-control association study with the cycloid psychosis subtype of SCZ in the German population using two methods for SNP genotyping. DESIGN AND METHODS: The SNPs were genotyped by direct DNA sequencing, as well as a novel one-label extension method. The results were analyzed for association with SCZ. RESULTS AND CONCLUSIONS: Significant association was found for SNPs rs1816071 and rs1816072 with SCZ susceptibility. This is consistent with our previous finding of association of SNPs in GABRB2 with SCZ susceptibility in Han Chinese. There was a total agreement between the genotyping results from one-label extensions and the results of direct DNA sequencing, thus validating the accuracy of the one-label extension method of SNP genotyping.

Adult↗

PubMed2006

Effects of a memory enhancing peptide on cognitive abilities of brain-lesioned mice: additivity with huperzine A and relative potency to tacrine.

Alzheimer's disease (AD) and related dementing disorders having cognitive manifestations represent an increasing threat to public health. In the present study, the effects of a memory enhancing NLPR tetra-peptide (MEP), huperzine A (Hup A), or a combination of the two on the cognitive abilities of brain-lesioned mice were evaluated and compared with tacrine in the passive avoidance and Y-water maze tests for the acquisition and retention aspects of cognitive functions. MEP at microg kg(-1) doses, and Hup A or tacrine at mg kg(-1) doses significantly reversed the cognition deficits induced by scopolamine. For acquisition ability, it was observed that mice administered with MEP (4.0 microg kg(-1)) spent less time escaping onto the platform in the water maze than those treated with tacrine (1.5 mg kg(-1)); whereas for memory retention, tacrine-administration resulted in a higher step-through latency in mice at the tested dose regime. In addition, co-administration of MEP (2.0 microg kg(-1)) and Hup A (0.1 mg kg(-1)) exhibited an additive effect resulting in considerable improvements in both acquisition and retention abilities of brain-lesioned mice. The results demonstrated that MEP was highly efficient in the rescue of cognitive abilities of brain-lesioned mice and in particular, the effective doses of MEP were about two orders of magnitude lower than that of tacrine, a therapeutic currently used in the treatment of AD. Moreover, MEP and Hup A were effective at reduced doses when the two were co-administered, providing a rationale for their combined usage in the treatment of cognitive deficits.

Alkaloids↗

PubMed2006

Anxiolytic-Like Effect of baicalin and its additivity with other anxiolytics.

Baicalin, a naturally occurring flavonoid, was previously reported to exert anxiolytic-like effects in the Vogel conflict test. In the present study, the anxiolytic effects of baicalin alone and in combination with other anxiolytics were tested in mice using the elevated plus-maze (EPM). Baicalin treatment (7.5 - 30 mg/kg) significantly increased entries into and time spent in open arms, indicative of an anxiolytic-like effect. Motor-depressive and myorelaxant side effects commonly associated with anxiolytics were not observed with baicalin at effective anxiolytic doses in the hole-board and horizontal wire tests, respectively. Co-administration of baicalin (3.75 mg/kg) with dl-tetrahydropalmatine ( dl-THP; 0.25 mg/kg), an anxiolytic-hypnotic alkaloid, both at sub-effective doses, induced an additive effect resulting in considerable anxiolysis. Similarly, an additive anxiolytic-like effect was observed with baicalin (3.75 mg/kg) and diazepam (DZ; 0.5 mg/kg). Results obtained from this study demonstrate the potential of baicalin as a candidate anxiolytic and its possible application in multidrug therapy. Abbreviations. BZS:benzodiazepine-binding site EPM:elevated plus-maze DZ:diazepam GABA (A):type A gamma-aminobutyric acid dl-THP: dl-tetrahydropalmatine.

Animals↗

PubMed2006

Effect of age on vascular beta2-adrenergic receptor desensitization is not mediated by the receptor coupling to Galphai proteins.

Beta-adrenergic receptor (beta-AR)-mediated vasorelaxation declines with age. In the vasculature, beta2-AR undergoes protein kinase A-mediated desensitization that causes a switch in the G protein coupled to beta2-AR; Galphai links instead of Galphas. We exposed Fischer 344 rat aortae of increasing age to a desensitizing dose of isoproterenol, and determined its effect on beta2-AR-mediated vasorelaxation. Desensitization decreased beta2-AR-mediated vasorelaxation in young aortae only. Subsequently, we used pertussis toxin to block Galphai to determine whether changes in beta2-AR/G protein coupling occurred. Galphai inhibition did not reverse desensitization or the age-related change, but there appears to be a population of beta2-AR linked to Galphai, as pertussis toxin treatment improved beta2-AR-mediated vasorelaxation in aortae from animals of all ages. These findings suggest aortic beta2-AR in older animals may be maximally desensitized, which would explain impaired vasorelaxation. Our results also imply that protein kinase A-mediated beta2-AR desensitization may not be responsible for the age-related decline.

Adenylyl Cyclases↗

PubMed2006

Segmental heterogeneity of epithelial ion transport induced by stimulants in rat distal colon.

Mammalian colon plays an important role in electrolyte and water balance, and exhibits significant segmental heterogeneity. The different responses to stimulants even exist in different segments of rat distal colon. The present study focus on the segmental heterogeneity of epithelial responses to different stimulants and investigates the possible mechanism by using short circuit current recording technique. Baseline I(SC) in the segment 4 of distal colon (DC(4), 20.8+/-2.8 microA.cm(-2)) was significantly lower than that in the segment 1 of distal colon (DC(1), 40.5+/-1.9 microA.cm(-2)). Basolateral application of indomethacin induced a larger reduction of the baseline I(SC) in DC(4) (-28.2+/-3.9 microA.cm(-2)) than that in DC(1) (-10.1+/-3.9 microA.cm(-2)). Moreover DC(4) are more sensitive to foskolin (a cAMP activator, apical side), Ach (basolateral side) and 5-HT (basolateral side) than DC(1), which was not affected by pretreatment with amiloride, a blocker of epithelial Na(+) channel. Basolateral pretreatment with atropine (muscarinic cholinergic receptor antagonist) for 10 min, Ach-induced DeltaI(SC) increases in both DC(1) and DC(4 )were totally blocked. Otherwise, 5-HT(4) receptor antagonist GR113808 (basolateral side) and SB-204070 (basolateral side) completely inhibited 5-HT-induced I(SC) increases in both DC(1) and DC(4). Taken together, the results suggested that the segmental heterogeneity of epithelial responses to different stimulants exists in rat distal colon. And it is more likely related to the dissimilar distribution of membrane proteins involved in the ion transports within different segments of rat distal colon.

Acetylcholine↗

PubMed2006

Apolipoprotein B gene 3'VNTR polymorphism: association with plasma lipids and coronary heart disease in Han Chinese.

BACKGROUND: Studies that considered polymorphisms within the apolipoprotein B (APOB) gene as risk factors for coronary heart disease (CHD) have reported conflicting results. METHODS: The phenotypic effects of the 3'VNTR polymorphism of the APOB gene on the susceptibility to CHD were investigated in 120 unrelated healthy individuals and 137 CHD patients. The internal structure of APOB gene 3'VNTR alleles was also analyzed by the methods of SspI restriction mapping and DNA sequencing of the allele fragments. RESULTS: In total, 14 segregating alleles and 32 genotypes of APOB gene 3'VNTR were characterized in the pooled total of 257 subjects. The frequency of 3'VNTR-B alleles [hypervariable element (HVE) > or =38)] in the CHD cases was higher than that of the controls (10.95% vs. 5.00%, p<0.05). 3'VNTR-B allele was dependently related to total cholesterol levels (p<0.05). Compared with SS homozygotes, 3'VNTR-B allele carriers were associated with an increased risk of CHD (OR=2.137, 95% CI=1.055-4.328, p=0.0349). No significant differences in the internal structure and sequences of APOB gene 3'VNTR alleles were found between cases and controls. CONCLUSIONS: APOB gene 3'VNTR polymorphism exerts an impact on lipid metabolism and may contribute to the susceptibility to the development of CHD in Han Chinese.

3' Flanking Region↗

PubMed2006

[Ssh10b2 differs from its paralogue Ssh10b in cellular abundance and the ability to constrain DNA supercoils].

The ssh10b and ssh10b2 genes, a pair of distantly related paralogues in Sulfolobus shibatae, encode members of the Sac10b DNA binding protein family in thermophilic archaea. It has been shown previously that Ssh10b exists in abundance in S. shibatae and is capable of constraining negative DNA supercoils, properties that are consistent with a speculated architectural role for the protein in chromosomal organization. In this study, the ssh10b2 gene was cloned and expressed in Escherichia coli, and the recombinant Ssh10b2 protein was purified to apparent homogeneity. Immunoblotting analysis using a specific anti - Ssh10b2 antibody showed that ssh10b2 was expressed in S. shibatae, but the cellular level of Ssh10b2 was only - 10% of that of Ssh10b. Recombinant Ssh10b2 was capable of interacting with both double-stranded and single-stranded DNA. The affinity of the protein for double-stranded DNA was higher than that reported for Ssh10b. The Ssh10b2 and Ssh10b proteins appeared to generate similar gel shift patterns on duplex DNA fragments. However, unlike Ssh10b, Ssh10b2 was unable to constrain DNA supercoils. These data suggest that Ssh10b2 does not serve as a general architectural factor in DNA compaction and organization in S. shibatae.

Archaeal Proteins↗

PubMed2006

[Structure analysis of apolipoprotein B 3' variable number of tandem repeats].

OBJECTIVE: To study the distribution, frequency and structure of variable number of tandem repeats (VNTR) in 3' region of apoB gene in Chinese population. METHODS: Genomic DNA was extracted from peripheral blood obtained under consent from randomly-chosen 522 individuals who came to the hospital for physical examination, and used to screen for polymorphisms of 3' VNTR of the apoB gene by employing polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), gradient polyacrylamide gel electrophoresis, cloning and sequencing. RESULTS: Sixteen types of alleles of apoB 3oVNTR were identified, among which heterozygotes were more than homozygotes. The biggest allele is HVE58, and the smallest one is HVE22. HVE34 had the highest frequency (40.4%), followed by HVE32 (34.7%). This showed significant difference from the allelic distribution of other populations (Caucasian and Swedish). Through sequencing of 60 alleles, a new isomer (Y-A=ATAATTAAATATTT) and four new types of alleles were found. CONCLUSION: The Chinese population we studied had a higher frequency of small alleles and showed a difference in allelic structure and frequency distribution from European and American in this populations.

Adult↗

PubMed2005

Alu-associated enhancement of single nucleotide polymorphisms in the human genome.

Identifying features shaping the architecture of sequence variations is important for understanding genome evolution and mapping disease loci. In this study, high-resolution scanning of Alu-centered alignments of the human genome sequences has revealed a striking elevation of the frequency of single nucleotide polymorphisms (SNP) in the body and tail of Alu sequences compared to flanking regions. This enhancement in SNP density is evident for all twenty-four chromosomes, and in both the Alu-body and Alu-tail, which together may be referred to as the Alu-SNPs. Reduced levels of Alu-SNPs in the sex chromosomes, especially in the non-recombining NRY region of the Y chromosome, are consistent with recombination events playing an important role in the enhancement. The Alu elements are unstable recombination-mutation hotspots in the human genome, and it is suggested that the Alu-SNPs represent a key manifestation of this instability. Variations in Alu-SNPs among the HapMap populations of northern and western European ancestry (CEU), Han Chinese from Beijing (CHB), Japanese from Tokyo (JPT), and Yoruba from Ibadan, Nigeria (YRI) indicate that the Alu-SNPs provide useful sequence markers, in addition to the Alu-insertion polymorphisms themselves, for the delineation of human genome evolution. That Alu-SNP levels are highest in the youngest Alu-Y, intermediate in the Alu-S of intermediate age, and lowest in the oldest Alu-J is consistent with the occurrence of not only genetic drift but also natural selection on the Alu-SNPs. Such evolutionary selection in turn suggests that Alu-SNPs might include potential sites of disease association, and therefore deserve detailed investigation.

Alu Elements↗

PubMed2005

Energetic quaternary salts containing bi(1,2,4-triazoles).

New energetic salts (2, 3, 9, 10, and 11) were synthesized via the protonation of 4,4'-bi(1,2,4-triazole) or N-4-(1,2,4-triazole)-N-3-(4-methyl-1,2,4-triazole)amine with nitric acid or perchloric acid or 5-nitro-tetrazole. The structures of 4,4'-bi(1,2,4-triazolium) nitrate (2), N,N-dimethyl-N'-(5-methyl-tetrazole)methanimidamide (8), and N-4-(1,2,4-triazole)-N-3-(4-methyl-1,2,4-triazolium)amine perchlorate (10) were confirmed by a single-crystal X-ray analysis. The physical properties and heats of combustion of the new ionic salts were measured, and the heats of formation were also determined.

Journal Article↗

PubMed2005

Congruence of evidence for a Methanopyrus-proximal root of life based on transfer RNA and aminoacyl-tRNA synthetase genes.

Among 60 organisms, the intraspecies genetic distances between tRNAs cognate for different amino acids, between the initiator and elongator tRNAs for Met, and between potentially paralogous pairs of aminoacyl-tRNA synthetases are found to be at a minimum within the Methanopyrus kandleri genome. These results indicate an exact congruence between the evidence from tRNA and aminoacyl-tRNA synthetase genes locating the root of life closest to this organism.

Amino Acids↗

PubMed2005

Energetic azolium azolate salts.

Energetic salts comprising substituted imidazolium and 1,2,4-triazolium cations and 4,5-dinitro-imidazolate and 5-nitrotetrazolate anions were synthesized and characterized. On the basis of experimentally obtained heats of combustion, the calculated heats of formation range from deltaHf(o) degrees = 80 (3) to 1071 kJ/mol (13). Imidazolate salts are more dense but have lower heats of formation than their tetrazolate analogues. Salts 4, 5, 8, and 11-14 fall into the ionic liquid class (mp < 100 degrees C). The structure of 1,2,4-triazolium 5-nitrotetrazolate (10) was confirmed by X-ray analysis.

Journal Article↗

PubMed2005

Cysteine mutants of human apolipoprotein A-I: a study of secondary structural and functional properties.

Apolipoprotein A-I(Milano) (A-I(M)) (R173C), a natural mutant of human apolipoprotein A-I (apoA-I), and five other cysteine variants of apoA-I at residues 52 (S52C), 74 (N74C), 107 (K107C), 129 (G129C), and 195 (K195C) were generated. Cysteine residues were incorporated in each of the various helices at the same helical wheel position as for the substitution in A-I(M). The secondary structural properties of the monomeric mutants, their abilities to bind lipid and to promote cholesterol efflux from THP-1 macrophages, and the possibility of antiperoxidation were investigated. Results showed that the alpha helical contents of all of the cysteine mutants were similar to that of wild-type apoA-I (wtapoA-I). The cysteine variant of A-I(M) at residue 173 [A-I(M)(R173C)] exhibited weakened structural stability, whereas A-I(G129C) a more stable structure than wtapoA-I. A-I(G129C) and A-I(K195C) exhibited significantly impaired capabilities to bind lipid compared with wtapoA-I. A-I(K107C) possessed a higher capacity to promote cholesterol efflux from macrophages than wtapoA-I, and A-I(M)(R173C) and A-I(K195C) exhibited an impaired efflux capability. Neither A-I(M)(R173C) nor any other cysteine mutant could resist oxidation against lipoxygenase. In summary, in spite of the similar mutant position on the helix, these variants exhibited different structural features or biological activities, suggesting the potential influence of the local environment of mutations on the whole polypeptide chain.

Antioxidants↗